Patents Assigned to Boehringer Ingelheim (Canada) Ltd.
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Patent number: 6313095Abstract: Disclosed herein are tetrapeptide derivatives of the formula X—NH—CHR1—C(W1)—NR2—CH[CH2C(O)—Y]—C(W2)—NH—CH[CR3(R4)—COOH]—C(W3)—NH—CHR5—Z wherein X is a terminal group, for example, alkanoyl or phenylalkanoyl radicals, R1 and R5 are selected from amino acid or derived amino acid residues, R2 is hydrogen, alkyl or phenylalkyl, R3 and R4 are hydrogen or alkyl or R3 and R4 are joined to form a cycloalkyl, W1, W2and W3 are oxo or thioxo, Y is, for example, an alkoxy or a monosubstituted or disubstituted amino, and Z is a terminal unit, for example, hydrogen, COOH or CH2OH. The derivatives are useful for treating herpes infections.Type: GrantFiled: October 6, 1994Date of Patent: November 6, 2001Assignee: Boehringer Ingelheim (Canada), Ltd.Inventors: Julian Adams, Pierre Louis Beaulieu, Robert Déziel, Neil Moss
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Patent number: 6306580Abstract: The present invention relates to a method for isolating cloned papillomavirus E1 protein from a eukaryotic expression system having demonstrable and reproducible viral helicase activity and preparation containing essentially pure E1 protein. The invention further relates to the use of this novel E1 protein preparation in a screening assay for identifying antiviral agents. More particularly a high throughput assay to screen for agents capable of inhibiting HPV DNA replication. The assay is based on measuring the effect of antiviral agents on the activity of the E1 protein and more specifically on its helicase activity.Type: GrantFiled: April 28, 1999Date of Patent: October 23, 2001Assignee: Boehringer Ingelheim (Canada) Ltd.Inventors: Alex Pelletier, Chris M. Farnet
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Patent number: 6268207Abstract: An enantiomeric-resolving process for obtaining (1R,2S)-1-amino-2-vinylcyclopropyl carboxylic acid methyl ester by use of an esterase, and especially Alcalase®, is disclosed.Type: GrantFiled: September 12, 2000Date of Patent: July 31, 2001Assignee: Boehringer Ingelheim (Canada) Ltd.Inventor: Murray D. Bailey
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Patent number: 6242439Abstract: A compound of formula I wherein R1 is hydrogen, methyl, ethyl, methoxy or methylthio; R2 and R3 each independently is hydrogen or lower alkyl; R4 is hydrogen, lower alkyl, methoxy, ethoxy or benzyloxy; R5 is lower alkyl, lower cycloalkyl, (CH2)mC(O)OR6 wherein m is the integer 1 or 2 and R6 is lower alkyl, phenyl optionally substituted; optionally Het or Het(lower alkyl); or R4 and R5 together with the nitrogen atom to which they are attached form a nitrogen containing ring optionally substituted with C(O)O-benzyl or with phenyl optionally substituted with C(O)OR7 wherein R7 is lower alkyl or (lower alkyl)phenyl; and Z is lower alkyl or optionally substituted phenyl or Het; with the proviso that when Z is (CH2)p-(Het), then R2 and R3 each is hydrogen; or a therapeutically acceptable acid addition salt thereof which compound is useful in the treatment of HCMV infections.Type: GrantFiled: October 6, 1998Date of Patent: June 5, 2001Assignee: Boehringer Ingelheim (Canada) Ltd.Inventors: Christiane Yoakim, Robert Déziel, Jeffrey O'Meara, William W. Ogilvie
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Patent number: 6239125Abstract: A compound of formula 1: wherein Y is S or O; R1 is C1-6 alkyl; (C0-6 alkyl)aryl; (C0-6 alkyl)Het; or R1 is an amino acid analog or dipeptide analog of the formula: wherein R2 is H, C1-10 alkyl; or an amide or ester group; A is C6-10 aryl, Het or CH—R3 wherein R3 is C1-6 alkyl or (C0-4 alkyl)aryl; and Z is H, C1-6 alkyl, or an acyl; R4 is hydrogen, lower alkyl, methoxy, ethoxy, or benzyloxy; and R5 is alkyl, cycloalkyl, carboxyl group; an aryl; Het or Het(lower alkyl); or R4 and R5 together with the nitrogen atom to which they are attached form a nitrogen containing ring optionally substituted with phenyl or C(O)OCH2-phenyl, said phenyl ring optionally mono- or di-substituted with among others C(O)OR7 wherein R7 is lower alkyl or phenyl(lower alkyl); or a therapeutically acceptable acid addition salt thereof which compounds are useful in the treatment of HCMV infections.Type: GrantFiled: October 6, 1998Date of Patent: May 29, 2001Assignee: Boehringer Ingelheim (Canada) Ltd.Inventors: Eric Malenfant, Jeffrey O'Meara, Robert Déziel, William W. Ogilvie
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Patent number: 6211170Abstract: A compound of formula I: wherein R1 is hydrogen, methyl, ethyl, methoxy or methylthio; R2 and R3 each independently is hydrogen or C1-3 alkyl; R4 is hydrogen, lower alkyl, methoxy, ethoxy, or benzyloxy; R5 is lower alkyl, lower cycloalkyl, (CH2)mC(O)OR6 wherein m is the integer 1 or 2 and R6 is lower alkyl, phenyl optionally substituted with C(O)OR7 wherein R7 is lower alkyl or phenyl (lower alkyl); or R6 is Het or Het(lower alkyl; or R4 and R5 together with the nitrogen atom to which they are attached form a nitrogen containing ring optionally substituted with benzyloxycarbonyl or with phenyl optionally substituted among other group with C(O)OR7 wherein R7 is lower alkyl or (lower alkyl)phenyl; X is selected from the group consisting of O, S, SO, SO2, NR8, wherein R8 is H or lower alkyl; and Y is C1-10 non-cyclic or cyclic alkyl; [(CH2)0-1]-phenyl, said phenyl ring optionally substituted; Het or Het(lower alkyl); or when X is NR8, wherein R8 is lower alkyl and Y is lower alkyl orType: GrantFiled: October 6, 1998Date of Patent: April 3, 2001Assignee: Boehringer Ingelheim (Canada) Ltd.Inventors: Christiane Yoakim, Robert Déziel, Stephen Kawai, William W. Ogilvie, Jeffrey O'Meara, Catherine Chabot
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Patent number: 6194143Abstract: Human cytomegalovirus (HCMV) protease is a slow-processing enzyme in vitro. Disclosed herein are improved fluorogenic and radiometric peptide substrates for CMV protease. The improved substrates have a Tbg-Tbg-Asn(NMe2) sequence replacing the Val-Val-Asn sequence, corresponding to the P4-P2 residues of the maturation site of the enzyme. The incorporation of this new sequence in a variety of substrates has afforded substrates with improved kinetic parameters compared to homologues containing the natural sequence only. For example, the substrate 2-aminobenzoyl-Tbg-Tbg-Asn(NMe2)-AlaiSer-Ser-Arg-Leu-Tyr(3-NO2)ARG-OH displayed a kcat/Km value of 15940 M-−1—s−1, i.e. over 60-fold greater than that of the equivalent, non-optimized substrate in identical conditions. The new substrates find use in assays which can evaluate and characterize HCMV protease inhibitors having low nanomolar potency.Type: GrantFiled: October 20, 1998Date of Patent: February 27, 2001Assignee: Boehringer Ingelheim (Canada) Ltd.Inventor: Pierre R. Bonneau
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Patent number: 6143715Abstract: Compound of formula (I) active against the Hepatitis C virus: ##STR1## wherein B is an acyl derivative; a is 0 or 1; R.sub.6, when present, is carboxy(lower)alkyl; b is 0 or 1; R.sub.5, when present, is C.sub.1-6 alkyl, or carboxy (lower)alkyl; Y is H or C.sub.1-6 alkyl; R.sub.4 is C.sub.1-10 alkyl; R.sub.3 is C.sub.1-10 alkyl; W is --NH--CH(R.sub.2)--C(O)--, wherein R.sub.2 is C.sub.1-6 alkyl; C.sub.6 or C.sub.10 aryl; C.sub.7-16 aralkyl; or carboxy (lower)alkyl; or W is a proline derivative; Q is a group of the formula --Z(R.sub.1)--C(O)--R.sub.13, wherein Z is CH or N; R.sub.1 is C.sub.1-6 alkyl or C.sub.1-6 alkenyl both optionally substituted with thio or halo,; and R.sub.13 is an activated carbonyl substituent, or Q is a phosphonate group of the formula --CH(R.sub.1)--P(O)R.sub.15 R.sub.16 wherein R.sub.15 and R.sub.16 are independently C.sub.6-20 aryloxy; and R.sub.1 is as defined above.Type: GrantFiled: August 10, 1998Date of Patent: November 7, 2000Assignee: Boehringer Ingelheim (Canada) Ltd.Inventors: Montse Llinas-Brunet, Murray D. Bailey, Teddy Halmos, Marc-Andre Poupart, Youla Tsantrizos
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Patent number: 5948935Abstract: Disclosed herein is a process for preparing (S)-.alpha.-amino-1-carboxycyclopentaneacetic acid which is a useful intermediate for preparing peptidomimetic inhibitors of herpes viral ribonucleotide reductase. The process comprises the preparation of the key intermediate ##STR1## and its subsequent conversion to the desired product.Type: GrantFiled: January 23, 1998Date of Patent: September 7, 1999Assignee: Boehringer Ingelheim (Canada) Ltd.Inventors: Jean-Marie Ferland, Ingrid Guse, Eric Malenfant
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Patent number: 5925762Type: GrantFiled: September 15, 1997Date of Patent: July 20, 1999Assignee: Boehringer Ingelheim (Canada) Ltd.Inventor: Bounkham Thavonekham
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Patent number: 5846941Abstract: Disclosed herein are peptidomimetic compounds of the formula A--B--D--CH.sub.2 CH{CH.sub.2 C(O)R.sup.1 }C(O)--NHCH{CR.sup.2 (R.sup.3)COOH}C(O)--E wherein A is a terminal group, for example an optionally substituted phenylalkanoyl, and B is a N-methyl amino acid residue; or A and B together form a saturated or unsaturated alkylaminocarbonyl; D is an amino acid residue; R.sup.1 is alkyl, cycloalkyl, a monosubstituted or a disubstituted amino; R.sup.2 is hydrogen and R.sup.3 is phenylalkyl, or R.sup.2 and R.sup.3 are joined to form a cycloalkyl; and E is a terminal unit, for example, an alkylamino or a monovalent amino acid radical such as NHCH(alkyl)C(O)OH. The derivatives are useful for treating herpes infections.Type: GrantFiled: June 5, 1995Date of Patent: December 8, 1998Assignee: Boehringer Ingelheim (Canada) Ltd.Inventors: Pierre Louis Beaulieu, Robert Deziel, Montse Llinas Brunet, Neil Moss, Raymond Plante
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Patent number: 5830864Abstract: Disclosed herein are peptide derivatives of the formulaA--B--NHCH{CH.sub.2 C(O)R.sup.1 }C(O)--NHCH{CR.sup.2 (R.sup.3)COOH}C(O)--Dwherein A is a terminal group, for example, an alkylaminocarbonyl or a phenylalkylaminocarbonyl; B is an amino acid residue; R.sup.1 is alkyl, cycloalkyl or a disubsubstituted amino; R.sup.2 is hydrogen or alkyl and R.sup.3 is alkyl, or R.sup.2 is hydrogen and R.sup.3 is phenylakyl, or R.sup.2 and R.sup.3 are joined to form a cycloalkyl; and D is a terminal unit, for example, an alkylamino or a monovalent amino acid radical such as NHCH(alkyl)C(O)OH. The derivatives are useful in treating herpes infections.Type: GrantFiled: July 17, 1995Date of Patent: November 3, 1998Assignee: Boehringer Ingelheim (Canada), Ltd.Inventors: Robert Deziel, Neil Moss, Raymond Plante
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Patent number: 5808085Abstract: A highly efficient and practical means has been developed which enables compounds of the formula: ##STR1## wherein R.sup.1 is lower alkoxy, lower alkylamino, di-(loweralkyl) amino, or the monovalent radical A--NR.sup.3, wherein A is lower alkyl or A is R.sup.4 R.sup.5 NC(O)CH.sub.2 wherein, for example, R.sup.4 is hydrogen or alkyl and R.sup.5 is hydrogen, alkyl or a substituted alkyl, or R.sup.5 is R.sup.6 R.sup.7 N-Alk wherein R.sup.6 and R.sup.7 each is hydrogen or lower alkyl and Alk is a divalent alkyl radical; R.sup.3 is, for example, benzyl, alkyl or a substituted alkyl; and R.sup.2 is, inter alia, alkyl, cycloalkyl, 1H-imidazol-4-yl, 4-thiazolyl or 2-amino-4-thiazolyl; to be prepared through the kinetic resolution of a compound of the formula: ##STR2## wherein R.sup.1 is as defined herein, R.sup.2 is as defined herein, and B is lower alkyl. These compounds are useful intermediates in the synthesis of renin inhibiting compounds.Type: GrantFiled: December 17, 1996Date of Patent: September 15, 1998Assignee: Boehringer Ingelheim (Canada) Ltd.Inventor: Murray Douglas Bailey
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Patent number: 5700780Abstract: Disclosed herein are peptide derivatives of the formula X?--NR.sup.1 --CH(R.sup.2)--C(W.sup.1)!.sub.n --NH--CR.sup.3 (R.sup.4)--C(W.sup.2)--NR.sup.5 --CH?CH.sub.2 C(O)--Y!--C(W.sup.3)--NH--CR.sup.6 --?CR.sup.7 --(R.sup.8)--COOH!--C(W.sup.4)--NH--CR.sup.9 (R.sup.10)--Z wherein X is a terminal group, for example, alkanoyl or phenylalkanoyl radicals, R.sup.1 is hydrogen, alkyl or phenylalkyl, R.sup.2, R.sup.4 and R.sup.10 am selected from amino acid or derived amino acid residues, R.sup.3, R.sup.5, R.sup.6, R.sup.7, R.sup.8 and R.sup.9 are hydrogen or alkyl, or R.sup.7 and R.sup.8 are joined to form a cycloalkyl, W.sup.1, W.sup.2, W.sup.3 and W.sup.4 are oxo or thioxo, Y is, for example, an alkyl or a cycloalkyl, Z is a terminal group, for example, COOH or CH.sub.2 OH, and n is 0 or 1. The derivatives are useful for treating herpes infections.Type: GrantFiled: October 11, 1995Date of Patent: December 23, 1997Assignee: Boehringer Ingelheim (Canada), Ltd.Inventors: Pierre Louis Beaulieu, Robert Deziel, Pierre Lavallee
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Patent number: 5693619Abstract: Disclosed herein is a method of using compounds of the formula:A-N(R.sup.1)C(O)CH.sub.2 CHR.sup.2 C(O)-Bwherein A is R.sup.3 R.sup.4 NC(O)CH.sub.2 when, for example, R.sup.3 is hydrogen or alkyl and R.sup.4 is hydrogen, alkyl or a substituted alkyl such as 2-(2-pyridinyl)ethyl, or R.sup.3 and R.sup.4 together with the nitrogen atom to which they are attached form a pyrrolidino, piperidino, morpholino or thiomorpholino; R.sup.1 is, for example, benzyl, alkyl or a substituted alkyl such as cyclohexylmethyl; R.sup.2 is, for example, alkyl, cycloalkylmethyl, 1H-imidazol-4-ylmethyl, 4-thiazolyl-methyl or (2-amino-4-thiazolyl)methyl; and B is a renin substrate transition state analog, for example, ?1(S)-(cyclohexylmethyl)-2(R),3(S)-dihydroxy-5-methylhexyl!amino for the treatment of congestive heart failure.Type: GrantFiled: February 1, 1996Date of Patent: December 2, 1997Assignee: Boehringer Ingelheim (Canada), Ltd.Inventors: Pierre LaVallee, Bruno Simoneau